Fibroblast Growth Factor 23 Predicts Mortality and End-Stage Renal Disease in a Canadian Asian Population with Chronic Kidney Disease

Abstract

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Biomarkers that predict end-stage renal disease (ESRD) and/or mortality could usher in new therapeutics to halt this onslaught. While fibroblast growth factor (FGF)23 can predict both ESRD and mortality, it has not been studied in North American CKD patients of Asian ethnicity. Method: This is a prospective investigation about the role of FGF23 in 998 Canadian patients of Asian descent with CKD defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/m² and followed up for 3 years. Results: The mean age of patients was 68.9 years and 68.3% were males. The mean (range) eGFR, and median FGF23 were 40.2 (11.0-59.0) mL/min and 154.1 (7.0-7,823.0) RU/mL, respectively. Over the 3 years, higher values of FGF23 levels at baseline were associated with higher risk of ESRD (hazard ratio [HR] for log[Fgf23] = 2.16 [95% CI 1.20-3.89]). Despite the short follow-up, 42 patients died due to cardiovascular diseases (38.8%), cancer (14.9%), and infections (12.7%). Log-FGF23 levels were independently associated with death, HR 1.94, 95% CI 1.24-3.03. Mortality risk increased in FGF23 subgroups from <100 to >400 RU/mL. In a time-changing covariate analysis, serial log-FGF23 levels over the 3 years predicted mortality with a HR of 2.66 (95% CI 1. 79-3.95). Conclusion: In a Canadian Asian population with CKD, FGF23 levels obtained at 6-monthly intervals for 3 years predicted ESRD and mortality suggesting that it is also a risk marker in Asians.

Factors associated with survival in dogs with chronic kidney disease

“…The univariable analysis is consistent with previous reports in cats and people . Importantly, this is the first report of an association between FGF‐23 and all‐cause death in dogs.…”

Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease

“…cFGF23 was independently associated with risk for all-cause mortality in our study. These findings are consistent with analyses examining the association between baseline FGF23 and risk for death [ 8 – 10 ]. In studies that have looked specifically at improvements in model discrimination with the addition of FGF23, there has been an improvement in outcome prediction and reclassification with the addition of this biomarker, suggesting that it may be a valuable tool for identifying those at greatest risk [ 29 ].…”

“…Three studies have sought to investigate change in FGF23 over time and the effect on risk for death in CKD patients [ 5 , 7 , 8 ]. The study by de Bouma et al showed that the rate of change in FGF23 was not predictive of mortality, whereas the study by Isakova et al demonstrated that rapidly rising FGF23 levels conferred an increased risk for death in comparison to stable levels.…”

The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis

“…Our findings are consistent with these previous findings that FGF23 is negatively correlated with the eGFR. Accumulating evidence has shown that increased FGF23 levels are strongly associated with an increased risk of adverse kidney outcomes or mortality in prospective studies on patients with CKD [13, 18, 52, 53]. This finding indicates that FGF23 may also have a prognostic value in these patients.…”